Prospects for increasing the accessibility of MRI.
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Biomedical subjects
Publications and source records attributed to L Kaufman.
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In 71 subjects (23 atopic patients, 22 hyperreactive patients and 26 normal test subjects) the authors twice performed a nasal provocation test with formaldehyde in three different concentrations. The test proved to be very much reproducible. There existed no clear-cut significant difference in the threshold for rhinorrhea, sneezing, tearing and pain in the three different groups. The difference in threshold for nasal blockade was very significantly different for the atopic and hyperreactive patients on one hand, and for the normal test subjects on the other hand. After the provocation a small increase in the mucociliary transport time was observed.
A non-radioactive fluorescent excitation analysis technique was used to measure total red blood cell volume in 31 unanaesthetised pig fetuses in utero. Red blood cell volume (y in ml) was closely related (r = 0.94) to fetal bodyweight (x in g): where y = 2.92 + 0.0291x. Average red blood cell volume was 34 +/- 1 ml kg-1 fetal bodyweight. Average estimated (total) blood volume was 117 +/- 3 ml kg-1 fetal bodyweight. It was concluded that this non-radioactive indicator dilution measurement of red blood cell volume is a significant advance over the established 51Cr method, and that measurement of red blood cell volume may be used to estimate fetal bodyweight in utero.
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In investigating six cases of blastomycosis in two school groups that had separately visited an environmental camp in northern Wisconsin in June 1984, we identified a large outbreak of the disease and isolated Blastomyces dermatitidis from soil at a beaver pond near the camp. Of 89 elementary-school children and 10 adults from the two groups, 48 (51 percent) of the 95 evaluated in September had blastomycosis. Of the cases, 26 (54 percent) were symptomatic (the median incubation period was 45 days; range, 21 to 106 days). No cases were identified in 10 groups that visited the camp two weeks before or after these two groups. A review of camp itineraries, a questionnaire survey, and environmental investigation showed that blastomycosis occurred in two of four groups that visited a beaver pond and in none of eight groups that did not. Walking on the beaver lodge (P = 0.008) and picking up items from its soil (P = 0.05) were associated with illness. Cultures of soil from the beaver lodge and decomposed wood near the beaver dam yielded B. dermatitidis. We conclude that B. dermatitidis in the soil can be a reservoir for human infection.
The feasibility of using expert systems for the development of analytical procedures is investigated. A system for the computer generation of procedures to determine active drug substances in commercial formulations is proposed. It is shown that in nearly 85% of the cases investigated the present system immediately yields a correct procedure or conclusion. It is concluded that selecting methods and developing procedures with the use of expert systems is difficult but feasible.
A recent study suggested that Chrysosporium species have the same diagnostic antigens as Histoplasma capsulatum and Blastomyces dermatitidis and, thus, compromise the antigenic identification of these pathogens. In light of these findings, studies were undertaken to determine the reliability of the exoantigen tests for identifying B. dermatitidis and H. capsulatum organisms from cultures. Sixty-three slant or shake culture extracts, or both, were derived from C. asperatum, C. keratinophilum, C. parvum, C. pruinosum, C. parvum var. crescens, Geomyces (Chrysosporium) pannorus, B. dermatitidis, and H. capsulatum. These were analyzed by use of a commercial exoantigen kit and exoantigen test reagents obtained from a commercial source. The results of these analyses were compared with those obtained with Centers for Disease Control reagents. Many of the extracts derived from nonpathogenic fungi produced nonspecific precipitin bands when reacted with the kit and reference antisera, particularly the B. dermatitidis antisera. None, however, produced antigens identical to the specific B. dermatitidis A and H. capsulatum H and M antigens. Our findings indicate that the properly controlled immunoidentification procedure is 100% specific for B. dermatitidis and H. capsulatum, and that cross-reacting antigens derived from morphologically similar saparophytic fungi do not pose identification problems.
Monoclonal antibodies (MAbs) of two different specificities were produced by immunizing mice with the semipurified M antigen of histoplasmin. One type, from clone CB4, was an immunoglobulin M that precipitated a polysaccharide present in histoplasmin and also formed immunoprecipitates with a cross-reactive polysaccharide present in extracts of Blastomyces dermatitidis and Coccidioides immitis. The second type of MAb, from clone EC2, was an immunoglobulin G that reacted in the enzyme-linked immunoelectrotransfer blot (EITB) assay with a doublet of proteins with an apparent molecular size of 70 to 75 kilodaltons. This molecule is proposed as the authentic M protein antigen that is recognized by M antibodies in sera from mice and rabbits immunized with Histoplasma capsulatum and from persons with histoplasmosis. The M factor also occurs in an abundant disulfide-bridged dimer which has a molecular size of 150 kilodaltons and is nonimmunoreactive under the conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
An enzyme-linked immunosorbent assay (ELISA) for blastomycosis was evaluated with 65 human sera from culturally or histologically proven cases of blastomycosis, 53 sera from humans with heterologous infections, and 115 sera from apparently normal people. The diagnostic value of the ELISA was compared with that of the widely used complement fixation (CF) and immunodiffusion (ID) tests. The assay gave a sensitivity of 80% and a specificity of 98% with a minimal positive titer of 1:16. In contrast, the CF and ID tests demonstrated sensitivities of only 40 and 65%, respectively, and both were 100% specific. It was concluded that ELISA titers of 1:32 or greater are indicative of active blastomycosis, whereas lower titers, which might represent cross-reactions, were considered suggestive of the disease. The specificity of low titers should be confirmed by immunodiffusion tests or from the study of serial serum specimens. Preliminary studies with sera from 6 dogs with active blastomycosis and 31 asymptomatic dogs revealed an ELISA sensitivity of 100% and a specificity of 97% when a 1:8 cutoff titer was used. Although a wide range of titers was obtained in both human and canine specimens, no single titer could be relied on to reflect the clinical form of disease. However, a four-fold-or-greater reduction in titer for serial specimens appeared indicative of a favorable prognosis.
A practical, sensitive, and specific immunodiffusion test was developed for diagnosing and monitoring pythiosis in horses. Culture filtrates, a soluble cell mass, and trypsinized Pythium sp. antigens were evaluated against prepared rabbit anti-Pythium sp. serum and pythiosis horse case sera. The culture filtrate antigens demonstrated the greatest capacity for detecting precipitins and the greatest stability during storage. In contrast, the trypsinized antigens had the weakest capability for detecting multiple precipitins and the poorest stability. The 13 sera from horses with proven active pythiosis were positive in immunodiffusion tests with the culture filtrate antigens. Each serum contained from three to six precipitins. Treated horses lost precipitins, and some became antibody negative. No false-positive reactions were noted in tests with sera from normal horses and humans or with sera from a variety of heterologous horse and human infections.
Three strains of mice were immunized with Candida tropicalis cell walls, and antibodies against mannan were detected by indirect enzyme immunoassay (EIA) in 3 of 9 BALB/c mice, 4 of 11 C57BL/6 mice, and 4 of 8 CFW mice. Responding mice produced immunoglobulin M (IgM), but IgG was not detected in their sera. Fusion of the high-responder BALB/c mouse with a plasmacytoma cell line resulted in 41 clones secreting antimannan monoclonal antibodies (MAbs). Four clones selected for propagation included one IgM and one IgG MAb that reacted with mannans of Candida albicans serotypes A and B and of C. tropicalis and two IgM MAbs specific for an epitope only in the mannans of C. albicans serotype A and C. tropicalis. One of the IgM MAbs, CB6, was an effective substitute for rabbit antibodies in the double-antibody sandwich EIA to detect antigenemia produced in rabbits infected with C. albicans A or C. tropicalis. It could function either as the peroxidase-conjugated indicator antibody or as the capture antibody. Two MAbs, CB6 (C. tropicalis and C. albicans A specific) and AC3 (C. tropicalis and C. albicans A and B specific), functioned in place of polyclonal antisera in the serotyping of C. albicans by immunofluorescence. There was 95.8% agreement in the results of serotyping using MAbs as reagents compared with rabbit antisera. Competitive inhibition in EIA between CB6 and monospecific antisera against C. albicans factors 1, 4, and 6 indicated that CB6 binds to an epitope which is probably factor 6. Serologic similarity between factor 4 and the binding site of MAb AC3 was also determined.
Section thickness in two-dimensional Fourier transform (FT) imaging is dependent on gradient strength and the shape of the radio-frequency pulses used to excite the nuclei. By manipulation of these parameters, it is possible to obtain 2.5-mm-thick sections in contiguous, multisection imaging. Because this method is efficient in imaging with long repetition times (TR), it effectively complements three-dimensional FT thin-section imaging techniques, which require imaging with short TRs. Fifteen double-echo, contiguous images of 0.9 X 0.9 X 2.5-mm resolution were obtained in 17.1 minutes for a TR of 2 seconds.
Conjugation can be used to synthesize half of the data acquired during a conventional two-dimensional Fourier transform imaging procedure, thus reducing imaging time by nearly half. The images acquired by this process have the same object contrast and spatial resolution as conventional images do, but with a 40% reduction in the signal-to-noise ratio (S/N). Conjugation can be used to advantage in magnetic resonance imaging units in which S/N levels are higher than needed to permit imaging with a single acquisition of each projection.
Using a new enzyme immunoassay (EIA) and standard immunodiffusion (ID) and complement fixation techniques for antibody to the A antigen of Blastomyces dermatitidis, we tested serum from 27 patients with blastomycosis diagnosed histopathologically or by culture; 20 with diagnoses made during 1981 through 1983 (Group A) and 7 during 1974 through 1976 (Group B). We also studied 30 control subjects with Mycoplasma pneumoniae infection (17 subjects), histoplasmosis (6 subjects), coccidioidomycosis (1 subject) and no known disease (6 subjects). Detectable antibody by all 3 tests was present more often for Group A than for Group B, possibly because of delay in testing. Enzyme immunoassay was the most sensitive test; a 1:8 or greater titer was present in acute-phase serum of all Group A patients tested, and a 1:64 or greater titer was associated with disseminated disease (p = 0.003). A positive ID was also more common in disseminated (88%) than in localized (33%) disease. Enzyme immunoassay titers of 1:16 were present in 4 control subjects, 3 with histoplasmosis. The 100% predictive values of a negative EIA and positive ID suggest that these tests are useful for serologic screening (EIA) and serologic confirmation (ID) of suspected blastomycosis, particularly in disseminated disease. Enzyme immunoassay titers of 1:32 or greater strongly support the diagnosis and titers of 1:16 or less may indicate localized disease or be nonspecific. None of the serologic tests predicted disease progression or reactivation.
A diagnosis of systemic zygomycosis made by fine needle aspiration of a kidney abscess was confirmed with a serum enzyme immunoassay for Zygomycetes. The serum immunoassay may provide a method for rapid diagnosis and obviate major invasive diagnostic procedures in establishing the diagnosis of zygomycosis.
Phase-sensitive imaging was used to correlate signal distribution with phase shift and velocity distribution in spin-echo magnetic resonance imaging (MRI). Flow-dependent, changing intensity patterns that were seen in a constant-flow phantom study were explained by the simultaneous effects of inflow signal enhancement, first-echo dephasing, and outflow signal loss occurring during laminar flow. In clinical studies, first-echo dephasing was shown during laminar flow in the inferior vena cava. Turbulent flow was demonstrated in the descending thoracic aorta during late systolic flow, and turbulent dephasing-rephasing was shown in the abdominal aorta.
Phialophora verrucosa and P. americana, two dematiaceous hyphomycetes, are known to cause chromoblastomycosis. Even though most medical mycologists consider P. americana as synonymous with P. verrucosa, others maintain them as two distinct species on the basis that the phialides of P. americana have deeper collarettes than those of P. verrucosa. Thirty-two isolates, identified either as P. americana or P. verrucosa, were studied for their morphologic, physiologic, and antigenic characteristics to evaluate their taxonomic status. Collarette morphology was found to be a variable character in 12 of the 32 isolates. Those 12 produced phialides with both shallow and deep collarettes. All of the isolates hydrolysed urea within 7 days at 25 degrees C, and failed to liquefy gelatin after 3 weeks at 25 degrees C. None of the isolates decomposed casein, xanthine, or hypoxanthine at the end of 3 weeks at 25 degrees C. All decomposed tyrosine. They grew at 25 degrees C and 37 degrees C, but failed to grow at 40 degrees C. The antigenic relationship between the two species was studied by the exoantigen procedure. The 32 isolates showed close antigenic relatedness. Adsorptions of antisera with homologous and heterologous antigens rendered the antisera free of precipitin bands when studied by the microimmunodiffusion test. The depth of phialide collarettes produced by the two species, being found to be variable character, and the identical nature of the two species with respect to their physiologic and antigenic characteristics, led us to conclude that P. americana should be considered as a synonym of P. verrucosa.